Mechanisms of demyelination are investigated in virus induced demyelinating diseases, i.e., canine distemper and mouse hepatitis virus encephalomyelitis. The goal is to determine whether demyelination in these conditions is due to: 1) Direct cytotoxic effect of virus on myelin supporting cells, 2) Immune reaction directed against virus laden myelin supporting cells, 3) Induction of an autoimmune reaction directed against myelin sheaths. Virus localization during the early stages of the disease prior to demyelination with particular reference to virus interactions with plasma membranes is determined by electron microscopy. Patterns of demyelination are compared to those seen in allergic encephalomyelitis. The effect of antibodies on virus infected cells and myelinated organ cultures, myelin lamellae and oligodendrocytes are explored in vitro and expected to contribute to mechanisms responsible for virus persistence. BIBLIOGRAPHIC REFERENCES: Welsh, R.M., Lampert, P.W., Burner, P.A., Oldstone, M.B.A.: Antibody Complement Interactions with Purified Lymphocytic Choriomeningitis Virus, Virology, 73, 59-71, 1976. Lampert, P.W., Joseph, B.S., Oldstone, M.B.A.: Antibody-Induced Capping of Measles Virus Antigens on Plasma Membrane Studied by Electron Microscopy. J. Virol. 15, 1248-1255, 1975.